The effect of hyperoxia on the lungs of rats deficient in essential fatty acids

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.(Murakami R, Obara H, Momota T et al.: The effect of hyperoxia on the lungs of rats deficient in essential fatty acids. J Anesth 3: 149–154, 1989)     

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.     

CELL PROLIFERATION AND CYTOKINE INDUCTION BY TNF-�� OF PSORIATIC KERATINOCYTES ARE NOT DIFFERENT FROM NORMAL KERATINOCYTES IN VITRO

Background:

Recent studies indicate that various cytokines including tumor necrosis factor-α (TNF-α) play an essential role in the induction and maintenance of psoriatic lesion.

Aims:

To compare the cell proliferation of keratinocytes by various cytokines and TNF-α-induced cytokine secretion among normal keratinocytes, uninvolved, and involved keratinocytes.

Methods:

The keratinocytes from normal skin, uninvolved, and involved psoriasis were cultured in the presence of IL-6, IL-8, epidermal growth factor (EGF), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α) epiregulin, amphiregulin, and TNF-α and then MTT assay for keratinocytes proliferation was performed. Furthermore, TNF-α-induced secretion of IL-6, IL-8, EGF, HGF, TGF-α, epiregulin, and amphiregulin were compared among these keratinocytes.

Results:

IL-6, IL-8, EFG, TGF-α, epiregulin, and amphiregulin, but not TNF-α increased keratinocyte proliferation of normal, psoriatic uninvolved, and involved skin. The increased cell proliferation by these cytokines and growth factors were not different among the keratinocytes derived from normal skin, uninvolved, and involved psoriasis. The significant induction of TNF-α increased IL-6, IL-8, EGF, HGF, TGF-α, epiregulin, and amphiregulin, but the increase in these cytokines and growth factors were not different among normal skin, uninvolved, and involved psoriasis.

Conclusion:

Cell proliferation by various cytokines and growth factors and TNF-α-induced cytokine secretion are not different between normal and psoriatic keratinocytes.     

Global gene expression analysis of keloid fibroblasts in response to electron beam irradiation reveals the involvement of interleukin-6 pathway

Keloid is a dermal fibroproliferative lesion of unknown etiology that commonly recurs after surgical excision. Post-operative adjuvant electron beam (EB) irradiation has been successfully used to reduce keloid recurrences. To provide new insights into the molecular mechanism behind the effect of EB irradiation, we used a cDNA microarray screening of more than 5000 genes to assess early changes in gene expression between EB-irradiated and non-irradiated keloid and non-lesional dermal fibroblasts. Primary fibroblast cultures from keloid and associated non-lesional dermis obtained from five patients were exposed to 15 Gy EB irradiation and analyzed after 15 min incubation. Early response to EB irradiation showed that 96 (1.8%) genes were modulated 2-fold or more in keloid fibroblasts. Upregulated genes accounted for 29.2% (28 genes), whereas downregulated genes comprised 70.8% (68 genes), indicating a silencing of many genes in keloid fibroblasts after EB irradiation. Many of the downregulated genes play roles in the enhancement of cell proliferation and extracellular matrix production, whereas several of the upregulated genes involves in the promotion of apoptosis and extracellular matrix (ECM) degradation. Using emerging bioinformatic tools and further corroboration, the interleukin 6 (IL-6) signaling pathway was found to be mainly involved in EB irradiation response. We also showed co-expression of IL-6 and its specific receptor (IL-6Ralpha) in keloid fibroblasts that points to the existence of an IL-6 autocrine loop in these cells. These results suggested that at the molecular level, EB irradiation might hinder keloid formation by regularizing disturbances in the homeostatic equilibrium between inducer and inhibitor activities in the matrix system most likely through the IL-6 pathway. Our study provides clues for the molecular mechanism(s) behind the beneficial effect of EB irradiation in reducing keloid recurrences and may help develop alternative strategies for the therapy and prophylaxis of this lesion.     

Drug-induced hypersensitivity syndrome due to mexiletine associated with human herpes virus 6 and cytomegalovirus reactivation

A 66-year-old man developed a fever of 38 degrees C and generalized pruritic rash about one month after mexiletine hydrochloride administration for ventricular tachycardia. The rash appeared as edematous erythema and papules with purpura on the lower extremities. Liver dysfunction, leukocytosis, and atypical lymphocytes were also present. Elevated antibody titer against human herpes virus 6 (HHV-6) was detected during the course of the disease (1:20 -> 1:640). The patient was diagnosed as having drug-induced hypersensitivity syndrome (DIHS) due to mexiletine. Discontinuation of the mexiletine administration and systemic corticosteroid treatment led to a temporary improvement, but tapering the corticosteroid dose twice led to recrudescence. Simultaneous with the recrudescence, elevated antibody titers against HHV-6 and cytomegalovirus were detected, as well as viral DNA in the blood, suggesting that these two viruses may have been involved in the recrudescence. The patient died of myocarditis, most likely related to cytomegalovirus. Our case indicates that, in addition to HHV-6, other herpes viruses such as cytomegalovirus can be reactivated in DIHS and may modify the clinical disease activity.     

A case of photocontact urticaria induced by photodynamic therapy with topical 5-aminolaevulinic acid

Photodynamic therapy (PDT) with topical application of 5-aminolaevulinic acid (ALA) is a promising new treatment option for the management of various cutaneous malignancies. Generally, topical ALA-based PDT has relatively insignificant adverse effects of transient character; these include itching, stinging or burning pain and slight to moderate erythema. We describe the first case of photocontact urticaria induced by topical ALA-based PDT for the treatment of unilesional mycosis fungoides. Although the first treatment session resulted merely in mild erythema, the second PDT caused marked urticaria corresponding to the PDT-applied area with an intolerable stinging sensation. A photopatch test demonstrated that black light and visible light irradiation after topical ALA provoked an urticarial reaction in the patient's uninvolved skin. These observations suggested an allergic pathogenesis for the wheal formation induced by PDT with topical ALA in this case. Photocontact urticaria should be considered as a possible adverse effect in ALA-based PDT.     

Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.     

Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal mucinous carcinoma: case report and review of 49 cases of extramammary Paget's disease

BACKGROUND: Anogenital Paget's disease (PD) may be accompanied by varying degrees of epidermal hyperplasia. The histological changes can be reminiscent of fibroepithelioma of Pinkus. METHODS: We present a case of perianal PD associated with fibroepitheliomatous epidermal hyperplasia in a 76-year-old-man with an underlying rectal mucinous carcinoma. We also carried out a retrospective analysis of 51 biopsies from 49 cases of extramammary PD to see whether particular epidermal changes occur in association with PD in different anatomic locations. RESULTS: A tumor, 3 cm in diameter, was noted in the patient's perianal skin. Histologically, it was composed of anastomosing thin epithelial strands with follicular differentiation. Paget's cells were distributed in the epithelial strands of this tumor as well as in the surrounding epidermis and anal epithelia. In our series of extramammary PD, epidermis was hyperplastic in two of two perianal cases, 26 of 43 genital skin samples, and one of six axillary PD biopsies. The stroma beneath the hyperplastic epidermis tended to be rich in thin collagen fibers and fibroblasts. CONCLUSIONS: Anogenital PD was more frequently associated with epidermal hyperplasia than axillary PD. Fibroepitheliomatous hyperplasia may be induced by the altered stroma associated with PD.